A Phase 1 Dose Escalation Study of Seneca Valley Virus (NTX-010), A Replication-Competent Picornavirus, in Relapsed/Refractory Pediatric Patients With Neuroblastoma, Rhabdomyosarcoma, or Rare Tumors With Neuroendocrine Features

OBJECTIVES:

Primary

• To estimate the maximum-tolerated dose and/or recommended phase II dose of Seneca Valley virus-001 (NTX-010) when administered as a single infusion to pediatric patients with relapsed or refractory neuroblastoma, rhabdomyosarcoma, or rare tumors with neuroendocrine features (Wilms tumor, retinoblastoma, adrenocortical carcinoma, or carcinoid tumors). (Part A [completed])
• To confirm that there is viral replication in these patients following NTX-010 administration. (Part A [completed])
• To define and describe the toxicities of NTX-010 when administered on this schedule. (Part A [completed])
• To determine whether the number of regulatory T cells (as measured by flow cytometry) can effectively be reduced following administration of NTX-010 plus low-dose metronomic and intravenous cyclophosphamide. (Part B)
• To characterize the pharmacokinetics (time course of viral clearance) following NTX-010 administration in these patients.

Secondary

• To preliminarily define the antitumor activity of NTX-010 within the confines of a phase I study. (Part A [completed])
• To evaluate the development of neutralizing antibodies to NTX-010 following IV administration of NTX-010. (Part A [completed])
• To evaluate development of neutralizing antibodies to NTX-010 following the combination of NTX-010 and cyclophosphamide. (Part B)
• To investigate the presence and permissivity of occult circulating tumor cells prior to and after the initial intravenous administration of NTX-010.